Management of Antithrombotic Therapy in Patients Undergoing Invasive Procedures

Endoscopic sphincterotomy is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated risk factors for complications of this procedure and their outcomes. We studied complications that occurred within 30 days of endoscopic biliary sphincterotomy in consecutive patients treated at 17 institutions in the United States and Canada from 1992 through 1994. Of 2347 patients, 229 (9.8 percent) had a complication, including pancreatitis in 127 (5.4 percent) and hemorrhage in 48 (2.0 Percent). There were 55 deaths from all causes within 30 days; death was directly or indirectly related to the procedure in 10 cases. Of five significant risk factors for complications identified in a multivariate analysis, two were characteristics of the patients (suspected dysfunction of the sphincter of Oddi as an indication for the procedure and the presence of cirrhosis) and three were related to the endoscopic technique (difficulty in cannulating the bile duct achievement of access to the bile duct by "precut" sphincterotomy, and use of a combined percutaneous-endoscopic procedure). The overall risk of complications was not related to the patient's age, the number of coexisting illnesses, or the diameter of the bile duct. The rate of complications was highest when the indication for the procedure was suspected dysfunction of the sphincter of Oddi (21.7 percent) and lowest when the indication was removal of bile-duct stones within 30 days of laparoscopic cholecystectomy (4.9 percent). As compared with those who performed fewer procedures, endoscopists who performed more than one sphincterotomy per week had lower rates of all complications (8.4 percent vs. 11.1 percent, P=0.03) and severe complications (0.9 percent vs. 2.3 percent, P=0.01). The rate of complications after endoscopic biliary sphincterotomy can vary widely in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique, rather than to the age or general medical condition of the patients.

Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests. Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2272.